Phase II evaluation of nivolumab in the treatment of persistent or recurrent cervical cancer (NCT02257528/NRG-GY002)

Abstract

Purpose: Patients with persistent/recurrent cervical cancer following platinum-based chemotherapy have limited therapeutic options. The Gynecologic-Oncology-Group conducted a phase II trial to assess efficacy and tolerability of nivolumab, an immune checkpoint inhibitor, in persistent/recurrent cervical carcinoma.

Patients and methods: Key eligibility criteria included persistent/recurrent cervical cancer, failure of prior systemic therapy and ECOG PS 0-1. Nivolumab 3 mg/kg was given IV every 2 wk. until disease progression or intolerable toxicity. Response was assessed every 8 wk. for 6 months and every 12 wk. thereafter. The primary endpoints were objective response as assessed by RECIST 1.1. The study used a 2-stage group sequential design. PD-L1 expression was evaluated in tumor specimens by immunohistochemistry (IHC) using a combined-positive-score (CPS) cutoff of ≥1%.

Results: Of 26 enrolled patients with persistent/recurrent cervical cancer, 25 were evaluable for response/toxicity with a median age of 45. 36% had ECOG PS of 1, and 100% had received one prior systemic chemotherapy regimen. PD-L1 expression (≥1%) was identified in 77.3% of tumor samples. As of 03/05/19, all patients were off study treatment; median follow-up for survival status was 32 months (range, 2-41.5). There were 21 (84%) patients with a treatment-related adverse event (TRAE) and most were grades 1-2. Six (24%) patients had grade 3 TRAEs with 1 discontinuing nivolumab due to hepatic toxicity. No grade 5 TRAEs occurred, and 2 patients had grade 4 TRAEs. One confirmed partial response (4%; 90% CI, 0.4%-22.9%), duration of response 3.8 months. Thirty-six percent of patients had stable disease (SD) (9/25; 90% CI, 20.2%-54.4%); the median duration of SD was 5.7 months (range, 3.5-12.7). Estimated PFS and OS at 6 months were 16% and 78.4%, respectively.

Conclusion: Single agent nivolumab exhibited low antitumor activity and an acceptable safety profile in patients with persistent/recurrent cervical cancer previously treated with platinum-based chemotherapy.

Trial registration: ClinicalTrials.gov NCT02257528.

Keywords: Cervical neoplasms; Immune-checkpoint inhibitors; Immunotherapy; Nivolumab; PD-1.

Conflict of interest statement

Declaration of competing interest Dr. Santin received research grants from Puma, Immunomedics, Gilead, Synthon, Merck, Boehringer Ingelheim, Genentech and Tesaro and consulting fees from Merck and Tesaro. Dr. Michael Frumovitz received monies for consultancy positions at Stryker, Biom'Up and Genentech. He received grants/grants pending from AstraZeneca and Stryker, and also received payment for lectures, including service on speakers bureaus from Stryker. Dr. Warner Huh reports personal fees from Inovo outside the submitted work. Dr. Samir Naif Khleif received money for board membership through Advaxis. He also served as consultancy for BioLine Therapeutics, Cancer Panels, IO Biotechnologies, NewLink Genetics, Northwest Biotherapeutics, PDS, Syndax Pharmaceuticals, UbiVac, Incyte, AratingoBio, CanlmGuide, Kahr Medical and McKinsey Medical. He has stock/stock options from Advaxis. He received research support from AstraZeneca, BioLine Therapeutics, Bristol-Myers Squibb, Merck, IO Biotechnologies, Lycera, MediImmune, Syndax Pharmaceuticals and KAHR Medical. Dr. Elena Ratner received monies from Tesaro and Genentech for advisory board membership. She also served as a consultant for Zai Labs, Covidient. She provided expert testimony. Dr. Roisin O'Cearbhaill reports personal fees from Clovis, Tesaro and GlaxoSmithKline outside the submitted work. Dr. Amir Jazaeri served as a consultancy for Gerson and Lehrman Group, Guidepoint, and Iowance Advisory Board Meeting. Dr. Jazaeri also has grants/grants pending from AstraZeneca, BMS, Iovance, Aravive, Pfizer and Immatics USA for clinical trial support. Dr. Jazaeri also received money from AstraZeneca for travel to Investigator's meeting. All other co-authors have no conflicts of interest to declare.

Copyright © 2019 Elsevier Inc. All rights reserved.

Figures

Figure 1.

A) Waterfall plot showing distribution of the best percentage change in the sum of target lesion size from baseline for an individual patient. The lines (−30 and + 20%) indicate the region with change from baseline that typically represent SD based on RECIST guidelines.

Figure 2.

Kaplan-Meier curves for progression-free survival and overall survival